The new compound MKC-442 is an NNRTI which has demonstrated potent in vitro activity against HIV-1 both as a single agent and in combination with other anti-HIV drugs. Data from in vitro studies have demonstrated antiretroviral activity of MKC-442 against various strains of HIV-1, including clinical isolates and strains with reduced sensitivity to ZDV. In the laboratory, combinations of MKC-442 with ddI produced moderate synergy while combination with ddC was additive in inhibiting HIV-1 infection. When used in combination with ZDV or with ZDV and saquinavir, impressive synergistic inhibition of HIV-1 replication was observed. When MKC-442 was combined with ZDV and 3 TC, the drugs synergistically suppressed HIV-1 replication in MT-4 cells over a wide range of doses. Since in vitro evidence indicates that strains of HIV-1 with reduced sensitivity to MKC-442 can emerge upon exposure to MKC-442 as a single agent, MKC-442 would be most effectively used in combination with other agents in the treatment of HIV-1 antiviral agents in the long-term treatment of HIV disease. This protocol aims to study the efficacy, safety, and tolerability of a combination of MKC-442 Viracept in the background of either stavudine (d4T) plus lamivudine (3TC) or stavudine (d4T) plus didanosine (ddI).